Vaccines have been administered to birds by injection intradermally, such as in the wing web, intramuscularly, such as in the breast muscle, or subcutaneously, such as in the neck. Administration intradermally in the wing web has always been limited to use with live vaccines, as only a small volume can be administered and, because live vaccines have to multiply after administration, it was thought that only they, by multiplication, presented sufficient antigen to achieve immunization. Larger quantities of vaccine can be administered subcutaneously and, most easily, intramuscularly, and these are the methods presently used for administering vaccines comprising inactivated antigens. The volumes administered by these means are normally 0.1 to 1 ml, most usually in the range of 0.2 to 0.5 ml. When administered in amounts of from 0.2 to 0.5 ml, avian vaccines commonly contain multiple inactivated immunogens. In some instances a live vaccine is mixed into an inactivated vaccine liquid formulation prior to administration. In which case the inactivated vaccine solution is used as the carrier. An example of such live vaccines are CAV vaccines, also referred to as chicken anemia agent (CAA) vaccines, as described in U.S. Pat. Nos. 5,686,077 and 5,728,569, which are included herein by reference. CAV has been shown to act like an immune modulator when combined with the inactivated vaccine.
In the poultry industry, immunizing by intramuscular or subcutaneous administration of inactivated vaccines has drawbacks. Dealing with large numbers of birds, it is desired to use the smallest amount of vaccine and a vaccine that is easy and safe to administer, and yet achieve satisfactory protection. With intradermal administration in the wing web, handling the birds in easier and the likelihood of a needle stick to the person during the vaccination is reduced. This is especially true when compared to subcutaneous administration in the neck, with which "self vaccination" is common, resulting in injury and sometimes loss of fingers from infection. Another goal is to reduce the volume of vaccine administered, which reduces the volume of vaccine that must be handled. This increases the number of immunizations that can be made from a given volume of vaccine.
A principal goal of the invention is the reduction of product damage; that is, damage to muscle tissue. Intramuscular, and even subcutaneous, injections to food animals can cause areas of inflammation, which result in stress to the animal and damage to the meat. A stressed animal will not feed or grow as well as a non-stressed animal. Moreover, using conventional amounts of vaccine the site of a localized immune response may remain as permanently damaged tissue. There is also the problem of vaccine retention, with vaccine remaining at the site of injection long after the vaccine is administered. For these reasons, the birds cannot normally be sold to the food industry.
Using the small volumes according to the invention minimizes localized inflammation and eliminates residual vaccine remaining at the site of injection.
Until the present invention, only live vaccines have been administered using intradermal administration to the wing web of chickens. Diseases for which this method has been used include Fowl Pox, Pigeon Pox, Fowl Cholera, Reo virus, Newcastle disease virus, Chicken Anemia virus (CAA or CAV) and Avian Encephalomyelitis (AE). The GRANT.TM. inoculator sold by International Inoculation Systems, Inc. of Cary, N.C., is advertised for wing web administration of vaccines in quantities of as little as 0.008 ml. These inoculators are described and claimed in U.S. Pat. No. 4,990,135, which is included herein by reference.
Prior to the present invention, inactivated vaccines have not been administered to the wing web because it has always been believed that inactivated vaccines must be administered subcutaneously or intramuscularly and with sufficient adjuvant in order to achieve an effective immune response. The small volumes used in wing web administration were not expected to accommodate a sufficient amount of adjuvant to present the immunogen for an adequate immune response and protective immunity.
We have discovered that inactivated vaccines can be administered intradermally into the wing web in volumes of from about 0.004 to about 0.08 ml with good results. Effective immunization can be accomplished administering these small volumes of vaccine if the total quantity of antigen per dose is at least one third the quantity in the large volumes previously used for administering inactivated vaccines by intramuscular means. Surprisingly, large quantities of adjuvant were not necessary for successful results.
When intradermal administration was used for live vaccines, it has always been necessary to separately vaccinate the same bird again in a different way if inactivated vaccines were to be administered. Reducing the number of immunizations each bird receives is a goal of significant economic interest. This is accomplished according to the invention by using a combination vaccine, which may contain both live and killed immunogens, administered via the wing web.